Human ceroid-lipofuscinosis is marked by blindness, dementia, ataxia and premature death. Models for this disease exist in English setters and sheep, whose clinical, pathological, and biochemical changes resemble the human disorder. In both syndromes autofluorescent lipopigments accumulate in the nervous system, viscera, retina and pigment epithelium. Soluble and membrane bound peroxide regulating enzymes have been determined in the normal and diseased canine retina and pigment epithelium. Isolated melanin granules showed high acid hydrolases and peroxidase activity. A chemical assay of superoxide free radicals has been developed and tested in various eye tissues. The pigment epithelium was most positive for the presence of these or related radicals. Leukocyte peroxidase was decreased in affected dogs whose electroretinograms were also decreased. Plasma glutathione peroxidase was also decreased. Rod outer segments were decreased in young sheep, and absent in adult animals. ERG studies showed that lipid hydroperoxides were toxic to the rabbit retina and piment epithelium, producing severe pathological changes. Retinal homogenates from affected dogs produced similar ERG changes. Tissue cultures have been establised for the dog and sheep models. These cells accumulate autofluorescent lipopigments that are electron dense and contain fingerprint patterns. Antioxidant treatment programs were initiated on 36 English setters.